Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dcl3 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO.
The polyomavirus enhancer binding protein 2alphaB (AML1/PEBP2alphaB/Cbfa2) plays a pivotal role in granulocyte colony-stimulating factor (G-CSF)-mediated differentiation of a myeloid progenitor cell line, 32Dc13. In this article, we report the identification of a PEBP2alphaB interacting protein, Ear-2, an orphan member of the nuclear hormone receptor superfamily that directly binds to and can inhibit the function of PEBP2alphaB. Ear-2 is expressed in proliferating 32Dc13 cells in presence of interleukin 3 but is down-regulated during differentiation induced by G-CSF. Interestingly, AML1/ETO(MTG8), a leukemogenic chimeric protein can block the differentiation of 32Dc13 cells, which is accompanied by the sustained expression of ear-2. Overexpression of Ear-2 can prevent G-CSF-induced differentiation, strongly suggesting that ear-2 is a key negative regulator of granulocytic differentiation. Our results indicate that a dynamic balance existing between PEBP2alphaB and Ear-2 appears to determine the choice between growth or differentiation for myeloid cells.
Ahn
M Y
MY
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606, Japan.
Huang
G
G
Bae
S C
SC
Wee
H J
HJ
Kim
W Y
WY
Ito
Y
Y
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; D011987:Receptors, Steroid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D011987:Receptors, Steroid; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor